Nitroalkyl substituted heterocyclic compounds and process for preparing them



Patented June 28, 1949 NITROALKYL SUBSTITUTED HETEROCY- CLIC COMPOUNDS AND PROCESS FOR PREPARING THEM Murray Senkus, 'Eerre Haute, Ind., assignor to Commercial Solvents Corporation, Terre Haute, Ind., a corporation of Maryland No Drawing. Application February 26, 1945, Serial No. 579,897

Claims. 1

My invention relates to new nitro amines and to a process for the preparation thereof. Specifically, these new compounds may be represented by the following structural formula:

X H T 6 A modification of the above procedure may freo z(|,alkyl uently be employed to advantage, and consists of alkyl reacting the desired amine with a suitable nitro wherein X represents a secondary amino radical alcohol- A solvent may be used if desired, but in 1 t f the group consisting f 1 general it will be found that a homogeneous soludyl, l-morpholyl, l-thiomorpholyl lupiperidyl tion can be obtained by agitating the mixture of (4 a1ky1) piperazyl and 1 (4 ary1) minemwl in amine and mtro alcohol. The products, produced which the carbon atoms ortho to the m atom by this process, are identical with those syntheare substituted by a group consisting of hydrogen Sized by the first mEntimPed melPhofi; hfaweveri h and alkyL mechanism of the reaction in its 1nit1al stages is AS examples of nitro amines coming within the materially different from that involved in the first scope of the above formula there may be menpmcedura thls cqnneciwm it has p tioned the following: N-(2--nitroisobutyl)piperi- Served that pllmaly mtlo 2110911015 In the dine; (zmitmisobutyl) 2,5 dimethylpyrmm presence of a substance appreciably basic 1n chardine; N-(Z-nitroisobutyl)-m0rpholine; N-(2-ni 20 acter decompose F formaldehyde the troisobutyl)thiomorpholine; N-(Z-nitroisobutyl) i from Whlch derived and m N phenylpiperazine; N (2 nitm 2 methylnbw Instances where the basic material happens to be tyl) N-methy1piperazine, d t 1 a primary or secondary amlne, the hberated This application is a continuation-in-part of formaldehyde reajcts therewith to q a my co-pendin application, Serial No. 455,931 droxymethynamme Compound whlch then filed August 24 1942, now abandoned acts with the nltroparafiin, produced by the de- Prior investigators in this field have found that Composltlon of F alcohol m the same primary nitropamflins would react with Nmmyn manner as described 1n the first procedure. The droxymethyl) dialkylamines; however, they also Fourse of the reactlon may be ,readfly arrived at the conclusion While making the illustrated by the following series of equations: aforesaid discovery, that N-(hydroxymethyl) N02 O2 monoalkylamines would not react with primary H0cH J a1k 1 HCalkyl+HOHO nitroparaflins, and that secondary nitroparaffins I 1 would neither react with N-hydroxymethyl my akyl mononor dialkylamines under any of the ex- Nlmamhol Nltmpammn Fmmaldehyde perirnental conditions which they had found to XH ECHO X CHOH 1 C clic Sech dro meth l 0 c1 on ilary amine Formaldehyde N ecolf ary a iiie 1c vious Workers also were of the opinion, in view of IITOQ their own experimental results, that neither pri- 40 X-CH20H H0alky1 z y1 mary nor secondary nitroparaifins would react akyl akkyl with condensation products derivable from form- N (hydmxymethyl) aldehyde and ammonia, formaldehyde and priy l c co d y mary alkylamines, formaldehyde and aniline, Ntmparafiin Cychc mmamme formaldehyde and diphenylamine, formaldehyde wherein X represents the substituent groups deand N-methylaniline, and numerous other prodfi p ms y. ucts of similar structure prepared from higher From an examination of the above series of molecular weight aldehydes, and primary or secequations it will be evident that although the ondary amines. starting materials are different from those used Contrary to that which would normally be exin the process first described, both procedures pected in View of the above prior art findings, may be considered equivalents of one another, however, I have discovered that nitro amines of since the compounds employed as starting matethe type described may be prepared by reacting rials in the first process are produced as interformaldehyde with a divalent cyclic amine in mediates in the second, after which said interwhich the amino nitrogen forms a part of the ring mediates react in a manner identical with the to form the corresponding N-(hydroXy-methyl) cyclic amine, which is in turn reacted With an equimolecular amount of a secondary nitroparaffin to produce a nitro amine of the type represented by the generic formula given above.

. 3 mechanism involved in the reaction forming the basis of the first mentioned method. Therefore, it is to be specifically understood that the appended process claims include both methods.

The preparation of these nitro amines by either of the above-mentioned methods, is preferably effected at temperatures of from about 2530 C.

Temperatures above this range may be used, but" in doing so care should be exercised to avoid temperatures which cause the formaldehyde to be volatilized from the reaction mixture. In some cases it may be desirable to carry out the reaction in a high pressure reaction vessel. Under such circumstances, substantially higher temperatures may be utilized without loss of formaldehyde, and decomposition of the reactants, or the reaction products.

The amines which may be employed in preparing these new compositions of matter are represented by the formula:

XH, wherein X represents the substituent groups defined previously.

Nitroparafiins that are operative in my process may be represented by the following formula:

alkyl alkyl Nitroparafiins typical of this class are Z-iiitr'obutane, Z nitropropa'ne, 2-nitrc'p'entane, and the like.

In reactions wherein nitro alcohols are employed instead of a nitro'parafiin and formaldehyde, the following are examples of typical nitro alcohols Which may be utilized: 2-nitro-2-rnethyl- .l-pro -anol, Z-nitro-Z-methyl-l butanol, 2-nitro- 2-etliyl-1-butanol, and the like.

The examples which follow are illustrative of the various types of nitro amines that come within the scope of the present invention. The examples are likewise illustrative of the procedures by which said products may be synthesized. It is to be specifically understood, however, that the following examples in no war-- limit the scope of my invention with respect to either the product or the. process, sincel have found that the reaction involved is very general in nature, and will occur, under the conditions described when reacting substantially any secondary hitroparaffin with a primary or secondary amine of the various types enumerated above.

Example I One mole of piperidine and one mole of 2- nitro-Z-methyl-l-propanol were placed, in a glassstoppered reaction vessel and the mixture was shaken until it had become homogeneous. The solution was allowed to stand at about 30 C. Water began to separate as a lower layer after about hours. After the separation of Water was substantially complete, the top layer containing the product was separated from the lower aqueous layer. Upon fractionation of the crude product, N-(Z-nitroisobutyl) piperidine was obtained, correspondin to a conversion of 83%. The nitrogen content found was 15.09% as compared to a theoretical calculated value of 15.05%. The product boiled at ZZ-83 C. at0.5 mm. pressure. U'nder standard conditions it was a solid having a melting point of 201 C.

Eaidmple If one mole of 2,5-dimethylpyrrolidine and one mole of 2-nitro-2 methyl-1-pr0pan0l were placed l-ated value of 13.99%.

in a glass-stoppered reaction vessel and the mixture was shaken until it had become homogeneous. The solution was allowed to stand at about 30 C. Water began to separate as a lower layer after about 1 0 hours. After the separation of water was substantially complete, the top layer containing the product was separated from the lower aqueous layer. Upon fractionation of the crude product, N-(Z-nitroisobutyl) -2,5-dimethylpyrrolidi ne was obtained, corresponding to a conversion of 46%. The nitrogen content found was 14.12% as compared to a theoretical calcu- The boiling point of the product was 70 C. at 0.5 mm. pressure and 11 was 1.4622- and 0120 was 0.9946.

Example III One mole of morpholine and one mole of 2- nitro-2--methyl-1-propanol were placed in a glassstoppered reaction vessel and the mixture was shaken until it had. become homogeneous. The solution was allowed to stand at about 30 C. Water began to separate as a lower layer after about 10 hours. After the separation of water was substantially complete, the top layer containing the product was separated from the lower aqueous layer. Upon fractionation of the crude product, N-(2-nitroisobutyl)morpholine was obtained, corresponding to a conversion of 24%. The nitrogen content of the product was found to be 14.78% as compared to a theoretical calculated value of 14.89%. The product was a solid having a melting point of 330 C.

Example I V 105 parts of 2,5-dimethylpyrrolidine were placed in a three=neclred reaction vessel equipped with stirrer, dropping funnel and thermometer. To this material in the vesselrwere added parts of a 35% aqueous formaldehyde solution while agitating. The temperature of the mixture was maintained below 50 C. by external cooling then parts of Z-nitropropane were added and the mixture was stirred at room temperature of about 25 C. for /2 hour whereupon 100 parts of ethyl ether were added and the mixture stirred. The mixture was then allowed to stand whereupon two layers separated. The non-aqueous layer was removed andfractionated. Fractionation resulted in 104 parts of N-(2-nitroisobutyl) -2,5-dimethylpyrrolidine boiling at 78-80 C. at 1 mm. gigeyssure and corresponding to a conversion of The nitro amines of my invention are in general ei-thercolorless liquids or white waxy solids. The lowemolecular weight nitro amines possess characteristic pungent odors, whereas the high molecular -weight nitro-amines are relatively odorless. The nitro amines are soluble in ether, methanol,- and benzene, but areinsoluble in water.

Some of the nitro amines of my invention have been found to be useful as toxicants in insect sprays. They are likewise useful as intermediatesin thepreparation of numerous organic compounds. Other uses of these products will readily occur to those skilled in the art.

Now having described my invention, what I claimis:

1. N- (2- nitroisobutyl) piperidine.

2. N -(2 nitroisobutyl) 2,5 4 dimethylpyrrolidine.

3. N-(2nitroisobutyl) morpholine.

4. In a process for thepreparation of N-(2-'-ni troisobutyl) piperidine,-, the steps which comprise forming a. homogeneous mixture of piperidine,

formaldehyde, and Z-nitropropane, permitting the mixture to stand under conditions avoiding loss of formaldehyde until the reaction is complete, and recovering said N-(2-nitroisobutyl)piperidine.

5. In a process for the preparation of N -(2-nitroisobutyl)-2,5-dimethylpyrrolidine, the steps which comprise forming a homogeneous mixture of 2,5-dimethylpyrrolidine, formaldehyde, and 2- nitropropane, permitting the mixture to stand under conditions avoiding loss of formaldehyde until the reaction is complete, and recovering said N- (2-nitroisobutyl) -2,5-dimethylpyrrolidine.

6. In a process for the preparation of N-(2-nitroisobutyl) morpholine, the steps which comprise forming a homogeneous mixture of morpholine, formaldehyde, and 2-nitropropane, permitting the mixture to stand under conditions avoiding loss of formaldehyde until the reaction is complete, and recovering said N-(Z-nitroisobutyl) morpholine.

7. In a process for the preparation of nitroamines of the formula:

N O: X-CHr--wlkyl alkyl wherein X is a secondary amino radical of the group consisting of l-pyrrolidyl, l-morpholyl, lthiomorpholyl, 1piperidyl, 1-(4-alkyl)piperazyl, and 1-(4-aryl)piperazyl, in which the carbon atoms ortho to the l-N atom are substituted by a group consisting of hydrogen and alkyl, the process which comprises forming a homogeneous mixture of substantially equimolar proportions of formaldehyde, an amine of the group consisting of pyrrolidine, morpholine, thiomorpholine, piperidine, 4-alkyl piperazine, and 4-aryl piperazine, in which the carbon atoms ortho to the l-N atom are substituted by a group consisting of hydrogen and alkyl, and a nitroalkane having the formula:

alkyl and allowing the mixture to stand under conditions avoiding any substantial loss of formaldehyde until the reaction has taken place, and recovering the nitroamine.

8. Nitroamines having the structural formula:

a kyl wherein X is a secondary amino group consisting of l-pyrrolidyl, l-morpholyl, l-thiomorpholyl, 1- piperidyl, 1(4-alkyl)piperazyl, and 1-(4-aryl) piperazyl, in which the carbon atoms ortho to the l-N atom are substituted by a group consisting of hydrogen and alkyl.

9. The process of claim '7 wherein the formaldehyde and the nitroalkane in said mixture are derived from the decomposition in situ of a nitroalcohol having the formula:

16. The process of claim '7 wherein the reaction is conducted at a temperature within the range of from about to C.

MURRAY SENKUS.

REFERENCES CITED The following referenlces are of record in the file of this patent:

Chemical Abstracts, 32, 494 (1938), citing: Cerf De Mauny-Bull. Soc. Chim. [5], 4, pages 1451-68 (1937). 

